There are various types of functional nucleic acid molecules, typified by relatively long functional RNA molecules such as antisense RNA, for example. Other typical examples of the functional nucleic acid molecules are relatively short functional RNA molecules such as shRNA (short hairpin RNA), siRNA (small interfering RNA), and miRNA (micro interfering RNA). These functional RNA molecules are generally known to contribute to down-regulation of gene expression. Various examples have been broadly reviewed as “interfering RNA” like in (Non Patent Literature 1).
An antisense RNA technique is excellent in target specificity. However, this technique has a disadvantage that an antiviral response in a cell is activated. In contrast, the technique using the relatively short functional RNA molecules such as shRNA does not activate the antiviral response practically. Instead, the relative short functional RNA molecules have the possibility of causing the off-target effects because it is difficult for short sequence length to keep high specificity to the target sequences. Thus, the relatively short functional RNA molecules tend to exhibit poor target specificity as compared with the antisense RNA technique.
Patent Literature 1 discloses a functional nucleic acid molecule (DNA molecule) comprising: a pol III type III promoter; a sequence identical or complementary to a target sequence that performs downregulation; and a 7SL small-RNA derived sequence (more specifically, a fragment of an Alu derived sequence) including at least binding domains to srp9 and srp14 proteins. The srp9 and srp14 proteins are members of a family of proteins that bind to a 7SL RNA in gene transcription to form a 7SL RNA complex.
It is described that the functional nucleic acid molecule disclosed in Patent Literature 1 is used as a gene expression downregulation technique in which an RNA molecule transcribed from the functional nucleic acid molecule practically causes no antiviral response activation and has excellent target specificity.
Alu is classified into one group of SINEs (Short Interspersed Elements). Note that the Alu derived sequence of the functional nucleic acid molecule disclosed in Patent Literature 1 is inserted in a particular orientation and considered to be involved in RNA stability.
On the other hand, it has been reported that some small RNA molecules can also enhance the level of transcription.